Milbemycin oxime is a vermifuge of the type of semisynthetic macrocyclic lactones, and is the oxime derivative of Milbemycins A3 and A4. Milbemycin oxime has the broad-spectrum effect of anti-parasitic. It has a good anti-parasitic effect against endoparasite, ectoparasite, especially nematode and arthropod. Lee et al's research of the mechanism of neuropharmacology of Milbemycin oxime on the vitro activity of Guangdong blood Strongylid and dog Dirofilaria shows that the inhibition and stimulation effects of Milbemycin oxime to the two types of parasites is performed by the gabergic and cholinergic mechanism. The drug combines with the locus on the target parasite cell with high specificity and affinity, affecting the permeability of the cytomembrane with respect to Cl—. Then, the releasing amount of γ-aminobutyric acid (GABA), which is an inhibitory neurotransmitter for the neurocyte of nematode and the myocyte of arthropod, increases. The Cl— channel controlled by glutamic acid opens. The permeability of the neurilemma with respect to Cl— is improved. GABA takes effect on the presynaptic nerve endings, decreasing the releasing of the excitatory transmitter, such that the subsynaptic membrane generates a weakened excitatory postsynaptic potential (EPSP). Since the depolarization of the membrane potential cannot reach the threshold, the postsynaptic neuron cannot enter the excitatory state, so as to cause inhibition. Thus, the parasite is paralyzed and dead. The main peripheral neurotransmission media of mammalia is acetyl choline, which will not be affected. Though this type of drug has a certain effect on GABA in central nervous system of the brain, it is not likely to pass through the Blood Brain Barrier. Thus, if used in a remanded dosage, it has no toxic or side effect on the vertebrate. After entering the body of a mammal, this type of drug rarely distributes among the brain tissue of the mammal. Thus, it can take effect on ectoparasite and endoparasite selectively, without affecting the animal host.
Literature reports of Milbemycin oxime mainly focus on the fermentation and strain breeding of Milbemycins. Literature reports of synthesizing Milbemycin oxime are rare. CN103896961A discloses a method for preparing a compound of the type of Milbemycin oxime. This method uses pyridinium chlorochromate as the oxidizer to conduct the oxidizing reaction. There are a lot of side reactions. The yield is low. Moreover, chromium trioxide used in the procedure is toxic, which is likely to cause heavy metal pollution.